The theme of this proposed Center is to investigate the etiology and pathogenesis of airway disease in children. We chose this theme for our program for the following reasons: 1) asthma and other forms of ainway disease are the most common chronic illnesses in children; 2) the environment results in unique combinations of exposures to children that affect lung immunity and consequently alters the risk of developing airway disease; 3) environmental models of airway disease provide an ideal opportunity to investigate basic mechanisms involved in the development of childhood airway disease; and 4) this theme builds on existing scientific expertise and relationships with community stakeholders and members to ensure a highly interactive program. Since ozone and endotoxin are common environmental exposures, and both of these agents have been demonstrated to have immune modulating affects, we have decided to use these relevant environmental exposures to further focus the projects in our proposed program. The end result is a highly integrated and focused Center that has the potential to make a number of novel, related observations. In aggregate, the coupled scientific findings from the proposed program will substantially enhance our understanding of ainway disease in children that can be immediately translated to communities in Colorado. The overarching hypothesis that unifies this research program is that lung host defense and lung immunity are dynamic biologically, are affected by ozone and endotoxin, and that this dynamic biology can alter susceptibility to agents known to cause airway disease in children. We believe that understanding the basic and translational aspects of this hypothesis will provide the scientific rationale to develop primary, secondary, and tertiary prevention programs that reduce the morbidity and mortality of childhood ain/vay disease/illnesses. Our PPG proposal includes three interactive projects (1 clinical and 2 basic), a Community Outreach and Translational Core, an Inhalation Toxicology Core, and an Administrative Core.